The present invention meets a need for a stereospecific synthesis of 5-phenyl-2S-pentanol from readily available optically pure starting material (S-ethyl lactate) which at the same time provides product readily purified and free of contaminating alcohols such as phenethyl alcohol or 3-phenylpropyl alcohol. Such contaminating alcohols are extremely difficult to remove; if not removed, these contaminants generally render the 5-phenyl-2S-pentanol unacceptable in the synthesis of CNS active agents such as levonantradol ##STR1## (Johnson, U.S. Pat. No. 4,260,764; Johnson et al., J. Clin. Pharmacol. 21, pp. 271S-282S, 1981; Milne and Johnson, ibid., pp. 367S-374S), since the contaminating alcohol carries through the synthesis of the levonantradol yielding a corresponding contaminant in the CNS agent, e.g., a compound having 2-phenylethoxy sidechain in place of the 5-phenyl-2-pentyloxy side-chain.
Levonantradol, derived from the present 5-phenyl-2S-pentanol, has found clinical use in man as an analgesic agent, Jain et al., ibid., pp. 320S-326S; and and as an antiemetic agent in cancer chemotherapy, Laszlo et al., ibid., pp. 48S-53S; Penta et al., ibid., pp. 11S-22S; Cronin et al., ibid., pp. 43S-50S; see also Johnson and Milne, U.S. Pat. No. 4,228,169.
The best stereospecific synthesis of 5-phenyl-2S-pentanol previously available employed the reaction of phenethyl magnesium halide with S-propylene oxide; it has been virtually impossible to form 5-phenyl-2S-pentanol free of phenethyl alcohol by this process, particularly on a large scale as required for commercial preparation of CNS agents such as levonantradol.
Certain intermediates employed in the present synthesis are known compounds, viz., methyl 2S-benzyloxypropionate, of the formula (VI) below, and 2S-benzyloxy-1-propanol of the formula (V) below. These compounds have been described by Mislow et al., J. Am. Chem. Soc., 84, pp. 1940-1944 (1962), the latter in deuterated forms. The first named compound was derived from S-ethyl lactate by reaction with benzyl bromide in alcohol in the presence of gross quantities of silver oxide, an extremely expensive reagent, a process to be contrasted with the present process which completely avoids this reagent. Reduction of methyl 2S-benzyloxypropionate with lithium aluminum deuteride by Mislow et al. gave 2S-benzyloxy-1-propanol-1-d.sub.2 ; the latter was converted to 2S-benzyloxy-1-propanol-1-d.sub.3 via its p-bromobenzenesulfonate ester, cf. compounds of the formula (IV) below.